Session Type: ACR Late-breaking Abstract Session
Session Time: 9:00AM-11:00AM
Background/Purpose: Upadacitinib (ABT-494, UPA), an oral,selective JAK-1 inhibitor was effective in 2 ph2 trials in rheumatoid arthritis(RA) pts with inadequate response (IR)/intolerance to csDMARDs/ bDMARDs.
Methods: Pts with active RA (TJC≥6, SJC≥6;hsCRP≥3 mg/L) on stable csDMARDs were randomized 2:2:1:1 to receive UPA15 mg or 30 mg once daily (QD) or PBO for 12 wks followed by UPA 15 mg or UPA30 mg QD starting at Wk 12. The primary endpoints were the proportion of ptswho achieved ACR20 and the proportion who achieved DAS28-CRP ≤3.2 at Wk12 (NRI).
Results: Of 499 randomized pts, 498 receivedstudy drug; 451 (90.6%) and 419 (84.1%) completed Wks 12 and 24 respectively. Baselinedisease characteristics indicated long-standing severe, refractory disease:(means) duration since diagnosis 13 yrs; DAS28CRP, 5.8; TJC68, 27.9; SJC66,16.8; 53% experienced ≥2 prior bDMARDs. At Wk 12, significantly more pts(p<.001) on UPA 15 and 30 vs PBO achieved the primary endpoints (ACR20: 64.6%and 56.4% vs 28.4%; DAS28-CRP≤3.2: 43.3% and 42.4% vs 14.2%) and othersecondary endpoints (Table 1). By Wk 1, significantly more pts achievedACR20 on UPA 15 and 30 vs PBO (27.4% and 24.8% vs 10.7%, p<.001). At Wk 12,significant improvements were observed on UPA 15 and 30 vs PBO for HAQ-DI (LSmean change -0.39 and -0.42 vs -0.17, p<.001). At Wk 24, responseswere similar or greater for pts originally on UPA and comparable for pts whoswitched to UPA after 12 wks of PBO.
In the first12 wks, frequency of AEs was comparable for PBO and UPA 15, but higher for UPA30 (Table 2). Overall AE rates (E/100 PY) through Wk 24 for UPA 30 weresimilar or slightly higher than UPA15; more AEs led to study drugdiscontinuation in UPA 30. Occurrence of infections was similar in all arms,but there were more serious infections and herpes zoster cases in UPA 30. Malignancieswere observed in 4 pts over 12 wks with 1 additional case through Wk 24.Through Wk 12, pulmonary embolism (PE) was reported in 2 pts (1 each on UPA 15and 30), none with DVT; through Wk 24, PE were reported in 4 more pts (UPA 15:3, 1 of whom also had a DVT; UPA 30:1). All had risk factors for DVT/PE. Twodeaths were reported (UPA 30: 1 prior to Wk 12; UPA 15:1 after Wk12).
Conclusion: In this treatment-refractory, bDMARD-IRRA population, rapid, significant improvements in signs and symptoms wereobserved with UPA at both doses vs PBO during 12 wks of treatment, andmaintained through 24 wks. No new safety signals were identified vs previousph2 studies. PE and DVT cases observed in this study have not been reported forthe only other ph3 study with unblinded data to date. Overall data from the ph3program will allow a comprehensive evaluation of the benefit:risk profile ofUPA in RA.
To cite this abstract in AMA style:Genovese MC, Fleischmann R, Combe B, Hall S, Zhang Y, Zhou Y, Mohamed MEF, Meerwein S, Pangan AL. Upadacitinib (ABT-494) in Patients with Active Rheumatoid Arthritis and Inadequate Response or Intolerance to Biological Dmards: A Phase 3 Randomized, Placebo-Controlled, Double-Blind Study of a Selective JAK-1 Inhibitor [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). http://acrabstracts.org/abstract/upadacitinib-abt-494-in-patients-with-active-rheumatoid-arthritis-and-inadequate-response-or-intolerance-to-biological-dmards-a-phase-3-randomized-placebo-controlled-double-blind-study-of-a-selec/. Accessed November 18, 2017.
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